One of the most important metabolic actions of insulin is to promote increased glucose uptake and utilization by the body. Impairment of this action of insulin (insulin resistance) has been associated with many common diseases such as diabetes, obesity, hypertension, and dyslipidemias. Currently, the "gold standard" method for measuring insulin sensitivity in vivo is the hyperinsulinemic euglycemic glucose clamp. This is a very labor intensive test that requires continuous infusions of insulin and glucose and multiple blood samples. An alternative method involves mathematical modeling of an intravenous glucose tolerance test (requires 30 blood samples over 3 hours). The purpose of this project is to develop a reliable method for measuring insulin sensitivity in vivo that is as accurate as currently available methods but simpler to implement. We hypothesize that the majority of the information needed to accurately estimate insulin sensitivity is contained in the fasting insulin and glucose levels as well as the insulin and glucose levels obtained shortly after an intravenous glucose load. We are testing this hypothesis by performing both hyperinsulinemic euglycemic glucose clamps as well as intravenous glucose tolerance tests on normal volunteers and groups of patients with diabetes, hypertension, or obesity. Data from these studies will be used to obtain estimates of insulin sensitivity by the glucose clamp method, minimal model method, and a novel analysis that utilizes only fasting and peak levels of glucose and insulin. We hope to devise a simpler method for determining insulin sensitivity in vivo that is suitable for testing large populations. This method will require only a few blood samples, take less than one hour to perform, and correlate with glucose clamp estimates at least as well as the minimal model method.